The overall objective of this project is to study human leukocyte elastase as a mediator of connective tissue injury, with special emphasis on the lung. Specific research goals for the coming year are: (1) Continued preparation of pure leukocyte elastase and chymotrypsin. (2) Studies on peptide-bond specificities and active-center structures of both proteases. (3) Studies on interactions of the enzymes with natural inhibitors and synthetic inactivators. (4) Electron- immunocytochemical localization of human lekocyte elastase. (5) Completion of project on the role of leukocyte elastase in the extracellular degradation of E. coli by human leukocytes. (6) Continuation of experiments dealing with the effects of these enzymes on alveolar architecture and on pulmonary surfactant proteins. (7) Study of degradation of rabbit airway cartilage proteoglycan by the purified leukocyte proteases. (8) Immunohistochemical study of human pulmonary alveolar macrophages and other lavage cells from post-mortem lungs, using antisera to human neutrophil leukocyte elastase.